Independent Inheritance of Cognition and Bipolar Disorder in a Family Sample

Background The basis of cognitive deficits in people with bipolar disorder (BD) has not been elucidated. These deficits may be the result of the illness or its treatment, but could also reflect genetic risk factors that are shared between BD and cognition. We investigated this question using empirical genetic relationships within a sample of patients with BD and their unaffected relatives. Methods Participants with bipolar I, II, or schizoaffective disorder (“narrow” BD, n=69), related mood disorders (“broad” BD, n=135), and their clinically unaffected relatives (n=227) completed tests of matrix reasoning, trail making, digit-symbol coding, semantic short-term recall, and affect recognition (DANVA2). General cognitive function ( g ) was quantified via principal components analysis (PCA). Heritability and genetic correlations were estimated with SOLAR-Eclipse. Results Participants with a “narrow” or “broad” BD diagnosis showed deficits in g, though affect recognition was not impaired. Cognitive performance was significantly heritable ( h2 = 0.322 for g, p<0.005). Coheritability between BD and cognition was small (coheritability for g & Narrow = 0.0184, for g & Broad = 0.0327) and healthy relatives of those with BD were cognitively unimpaired. Conclusions In this family sample, cognitive deficits were present in participants with BD, but social cognition, measured by affect recognition, was not impaired. Deficits were largely not explained by overlapping genetic determinants of mood and cognition. These findings support the view that cognition comprises separable social and non-social domains and that cognitive deficits in BD are largely the result of the illness or its treatment. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funded by the NIMH Intramural Research Program, grant 1ZIAMH002843 and protocol 80 M 0083. Human materials were collected by informed consent under protocol. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of the National Institute of Mental Health I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data and associated biological specimens are available to qualified investigators through dbGAP (phs000899.v1.p1)